In a study to evaluate the molecular interactions critical for oncogenic effects of over expression of the erbB-2 receptor in lung cancer, T antigen immortalized human bronchial epithelial cells were engineered to over express this receptor. Examination of tumorigenic and non- tumorigenic clones suggested the hypothesis that EGFR-erbB-2 heterodimers, formed under the influence of high autocrine production of TGF-alpha, were necessary for tumor formation. This hypothesis was supported by experiments in which a tumorigenic, high TGF-alpha producer, E6T, was transfected with an antisense TGF-alpha construct, creating a cell line, (E6TA), with a 95% reduction in TGF-alpha secretion and loss of tumorigenicity. In order to evaluate heterodimer formation, E6T and E6TA cells were studied for constitutive levels of erbB family receptors (erbB1-4). This study revealed that in this cell type, erbB-1 is the dominant receptor. Studies comparing the activation of signal transduction pathways downstream of these receptors indicate that, with no external growth factor addition, the MAPK and STAT3 pathways are differentially activated in the tumorigenic E6T when compared to E6TA cells.